The aim of our study was to emphasize the importance of accurate and standardized techniques for detailed monitoring of the microenvironment in multiple myeloma (MM). Bone marrow fibrosis, angiogenesis, and plasma cell infiltrates in bone marrow biopsy (BMB) samples at the time of diagnosis and on completion of therapy were analyzed for 42 patients with newly diagnosed MM. Computerized image analysis was used for all slides stained with anti-CD138 and anti-CD34. The patients with fibrosis in pretreatment BMB samples had significantly higher microvessel density (MVD) and plasma cell infiltrates. In posttreatment BMB samples, nonresponders had a significantly higher frequency and grade of fibrosis and higher values of MVD, total vascular area, and plasma cell percentage. The overall survival of nonresponders and patients with increased marrow fibrosis in posttreatment BMB samples was significantly shorter. The obtained results confirm that complex morphologic examination of the bone marrow microenvironment during the monitoring of MM can provide better prognostic significance.

BackgroundPrognostic and predictive significance of epidermal growth factor receptor (EGFR) in colorectal carcinomas (CRCs) is still controversial. The aim of the present study was to explore and correlate membrane and nuclear EGFR and cyclin-D1 protein expression with EGFR gene status of tumor cells.MethodsImmunohistochemical and FISH analysis was performed on 135 archival formalin fixed and paraffin embedded CRCs.ResultsStrong membrane and strong nuclear EGFR staining was detected in 16% and 57% of cases, respectively, and strong cyclin-D1 expression in 57% samples. Gene EGFR amplification was identified in 5.9% and polysomy in 7.4% of cases, while 87% showed no EGFR gene changes. A statistically significant difference was only found between tumor grade and expression of membrane EGFR, while nuclear EGFR and cyclin-D1 expression was not associated with the clinicopathologic characteristics analyzed. Tumor cells displaying gene amplification and strong protein membrane EGFR expression overlapped, while EGFR gene status showed no correlation with nuclear EGFR and cyclin-D1. There was no association between membrane EGFR and cyclin-D1, whereas nuclear EGFR expression was strongly related to cyclin-D1 expression.ConclusionsStudy results revealed heterogeneity among CRCs, which could have a predictive value by identifying biologically and probably clinically different subsets of tumors with the possibly diverse response to anti-EGFR therapies.

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deskriptori: transplantacija krvotvornih matičnih stanica; Hodgkinova bolest-liječenje; ne-Hodgkinov limfomliječenje; karmustin-nuspojave, terapijska primjena; Bendamustin-nuspojave, terapijska primjena; kombinirani protutumorski kemoterapijski protokoli-terapijska primjena; transplantacijsko kondicioniranje-metode; Mukozitis-etiologija; trombociti-djelovanje lijeka; autologna transplantacija sažetak. unatrag nekoliko godina u hematologiji i onkologiji globalno sve češći problem postaje prikladna opskrba "starijim i manje zanimljivim" kemoterapeuticima. Zbog povremene nestašice karmustina, jednog od osnovnih kemoterapeutika pri kondicioniranju prije autologne transplantacije krvotvornih matičnih stanica (atkS) u oboljelih od limfoma, u našem se centru od 2016. godine on zamjenjuje bendamustinom. u ovom radu retrospektivno analiziramo tijek atkS-a u 41 bolesnika koji su primili bendamustin u sklopu protokola BeeaM te ga uspoređujemo s tijekom atkS-a u 40 bolesnika koji su primili karmustin u sklopu protokola BeaM. Medijan oporavka vrijednosti neutrofila (> 0,5 × 10 9 /l) u skupini koja je primila bendamustin iznosio je 11 dana, dok je u skupini kondicioniranoj karmustinom iznosio 10 dana. Medijan oporavka vrijednosti trombocita (> 20 × 10 9 /l) bio je duži kod skupine koja je primala bendamustin (16 prema 13 dana) te su ti bolesnici bili duže ovisni o transfuzijama eritrocita (7 prema 5 dana). Infektivne komplikacije nisu bile češće nakon primjene bendamustina, ali smo nakon primjene karmustina imali veću pojavu mukozitisa II.-III. stupnja (35% prema 12%). nakon primjene bendamustina zabilježen je jedan slučaj nefrotoksičnosti i kardiotoksičnosti terapije, dok kod primjene karmustina te komplikacije nisu zabilježene. Pri upotrebi bendamustina kod kondicioniranja u naših bolesnika u ovom trenutku nije utvrđena znatnija hematološka toksičnost u odnosu prema karmustinu, ali su prisutni dulji period oporavka vrijednosti trombocita te niža incidencija mukozitisa. descriptors: Hematopoietic stem cell transplantation; Hodgkin disease-therapy; lymphoma, non-Hodgkin-therapy; Carmustine-adverse effects, therapeutic use; Bendamustine hydrochloride-adverse effects, therapeutic use; antineoplastic combined chemotherapy protocols-therapeutic use; transplantation conditioningmethods; Mucositis-etiology; Blood platelets-drug effects; transplantation, autologous summary. Inadequate supply of "old and less interesting" chemotherapeutic agents is becoming a global issue in hemato-oncology today. In 2016 we were faced with occasional carmustin shortage, one of the most commonly used in autologous transplant conditioning regimens for lymphoma in our centre, so we decided to use bendamustin instead. We performed a retrospective analysis of 41 patients treated at our centre who had received bendamustin within BeeaM protocol and compared them with 40 patients who had received carmustin within BeaM protocol. Both protocols were used as conditioning protocols before autologous stem cell transplantation. neutrophil recovery median following...

* korišten je Fisherov egzaktni test; ISS-internacionalni sustav stadija bolesti za mijelom; anemija-hemoglobin 20 g/L ispod donje granice normale (138 g/L za muškarce; 119 g/L za žene); § renalna insuficijencija (RI)-serumski kreatinin iznad gornje granice normale (117 mmol/L za muškarce; 96 mmol/L za žene)